The project in general is aimed at investigating the molecular mechanisms underlying the brain dysfunction associated with hypothyroidism during early life. Several ancillary advantages are attached to such an approach. Thus, experimental cretinism is a valuable model which not only may provide information on the of mental retardation in general, but also lead to insight on the molecular events occurring during normal brain development, the regulatory role of thyroid hormones in such processes, and their primary mode of action. Specific studies are designed to characterizethe regional and subcellular localization of specific, physiologically, relevant, receptor sites for thyroid hormones in the rat brain during development. A second aspect under investigation which represents an outgrowth of recent studies involves a quantitative and qualitative examination of membrane (synaptosomal) glycoproteins in developing hypothyroid rats by specific labelling of monosaccharide constituents and gel electrophoresis. BIBLIOGRAPHIC REFERENCES: Geel, S.E. and Gonzales, L.: In vitro studies of cerebral cortical RNA and nucleotide metabolism in hypothyroidism. J. Neurochem., 25:377, l975. Gonzalea, L. and Geel, S.E.: Thin layer chromatography of brain adenine nucleoside and nucleotides and determinaton of ATP specific activity. Anal. Biochem., 63:400, l975.